RGD Reference Report - Inhibition of hyperacute transplant rejection by soluble proteins with the functional domains of CD46 and FcgammaRII. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Inhibition of hyperacute transplant rejection by soluble proteins with the functional domains of CD46 and FcgammaRII.

Authors: Lanteri, MB  Powell, MS  Christiansen, D  Li, YQ  Hogarth, M  Sandrin, MS  McKenzie, IF  Loveland, BE 
Citation: Lanteri MB, etal., Transplantation. 2000 Mar 27;69(6):1128-36.
RGD ID: 9588604
Pubmed: PMID:10762218   (View Abstract at PubMed)

BACKGROUND: Recombinant soluble forms of complement regulatory molecules, including the human complement regulatory protein CD46 (rsCD46), have been shown to inhibit hyperacute transplant rejection (HAR) and protect against complement-mediated inflammatory tissue damage. Similarly, recombinant soluble forms of the immunoglobulin receptor FcgammaRII (rsFcgammaRII) can attenuate antibody-mediated inflammatory responses. We have produced and tested the function of novel recombinant chimeric proteins that incorporate the functional domains of both CD46 (membrane cofactor protein, MCP) and the low affinity human IgG receptor FcgammaRII (CD32). METHODS: Two recombinant soluble chimeric proteins (CD46:FcR and FcR:CD46) were designed and produced using a human cell expression system. Their ability to protect cells against complement-mediated lysis (through the CD46 domain) and bind human IgG (through the Fc receptor domain) was assessed in vitro. They were also tested in vivo in the rat reverse passive Arthus reaction and a murine model of hyperacute cardiac transplant rejection. RESULTS: In vitro, the functional domains of the chimeric proteins each retained their activity. In vivo, the serum half-life of the recombinant chimeric proteins in mice was more than either rsCD46 or rsFcgammaRII. In the rat reverse passive Arthus reaction, intradermal injection of each recombinant protein substantially reduced inflammatory skin edema (>50%) and polymorphonuclear neutrophil infiltration (>90%). In the hyperacute rejection model, i.v. treatment with FcR:CD46 prevented complement-mediated rejection, macroscopic bruising, edema, and thrombosis more effectively than rsCD46. CONCLUSIONS: CD46/FcgammaRII bifunctional proteins have an improved ability to control complement-mediated hyperacute graft rejection and have therapeutic potential in other conditions involving antibody-mediated inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumanarthus reaction treatmentIDA  RGD 
Fcgr2aRatarthus reaction treatmentISOFCGR2A (Homo sapiens) RGD 
Fcgr3Mousearthus reaction treatmentISOFCGR2A (Homo sapiens) RGD 
FCGR2AHumanTransplant Rejection treatmentIDA  RGD 
Fcgr2aRatTransplant Rejection treatmentISOFCGR2A (Homo sapiens) RGD 
Fcgr3MouseTransplant Rejection treatmentISOFCGR2A (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)

Objects referenced in this article
Gene FCGR2B Fc gamma receptor IIb Homo sapiens
Gene Fcgr2b Fc receptor, IgG, low affinity IIb Mus musculus
Gene Fcgr2b Fc gamma receptor 2B Rattus norvegicus

Additional Information